乳酸代谢重编程在非小细胞肺癌中的研究进展
Advances in Lactate Metabolic Reprogramming in Non-small Cell Lung Cancer
摘要
Abstract
Non-small cell lung cancer(NSCLC)is characterized by high incidence and mortality,with a low five-year survival rate.Lactate metabolism plays a central role in the metabolic reprogramming of NSCLC.Beyond serving as the end-product of glycolysis,lactate accumulates in the tumor microenvironment(TME),contributing to acidification,and can also enter the tricarboxylic acid cycle to participate in energy metabolism.Moreover,the G protein-coupled receptor 81(GPR81)/phosphoinositide 3-kinase(PI3K)/mammalian target of rapamycin(mTOR)signaling axis induces the expres-sion of immune checkpoint molecules,such as programmed death-ligand 1 and cytotoxic T lymphocyte-associated protein 4(CTLA-4),thereby suppressing the functions of T lymphocytes and natural killer cells and establishing an immunosuppressive microenvironment.Lactate further promotes epithelial-mesenchymal transition and tumor metastasis,and drives NSCLC che-moresistance and relapse via histone lactylation.Clinical studies indicate that enhanced lactate metabolism is associated with NSCLC progression and chemotherapy resistance,while targeting lactate metabolism in combination with immunotherapy exerts synergistic antitumor effects.Therefore,comprehensive inhibition of lactate metabolism together with enhancement of antitumor immunity may improve the efficacy of precision therapy in NSCLC.关键词
肺肿瘤/乳酸代谢/肿瘤微环境/表观遗传Key words
Lung neoplasms/Lactate metabolism/Tumor microenvironment/Epigenetics引用本文复制引用
周军,葛柳伶,蒋敬庭..乳酸代谢重编程在非小细胞肺癌中的研究进展[J].中国肺癌杂志,2026,29(2):141-149,9.基金项目
本文受国家生物制药技术创新中心省级人才计划(No.NCTIB2024JS0101)、国家自然科学基金项目(No.32270955)、江苏省重点研发计划专项资金项目临床前沿技术(No.BE2022719)、江苏省医学重点学科(No.YXZDXK202236)、常州市临床医学中心(No.CZZX202201)、常州西太湖细胞前沿技术发展基金会重点培育项目(No.2022-P-010)和常州市卫健委"十四五"高层次人才培养计划项目资助 This paper was supported by the grants from Provincial-level Talent Program for National Center of Technology In-novation for Biopharmaceuticals(No.NCTIB2024JS0101,to Jingting JIANG),National Natural Science Foundation of China(No.32270955,to Jingting JIANG),the Key R&D Project of Jiangsu Province(No.BE2022719,to Jingting JIANG),Jiangsu Provincial Medical Key Discipline(No.YXZDXK202236,to Jingting JIANG),Changzhou Clinical Medical Center(No.CZZX202201,to Jingting JIANG),Prospective Research Program of Changzhou Xitaihu Development Foundation for Fron-tier Cell-Therapeutic Technology(No.2022-P-010,to Jingting JIANG)and Top Talent of Changzhou"The 14th Five-Year Plan"High-Level Health Talents Training Project(to Jingting JIANG). （No.NCTIB2024JS0101）
